Amide bond formation: beyond the myth of coupling reagents (original) (raw)
Related papers
Immobilized Coupling Reagents: Synthesis of Amides/Peptides
ACS Combinatorial Science, 2014
The primary idea of using immobilized reagents in organic synthetic chemistry is to simplify the downstream process, product workup and isolation, and therefore avoiding timeconsuming and expensive chromatographic separations, which are intrinsic to every synthetic process. Numerous polymer-bounded reagents are commercially available and applicable to almost all kinds of synthetic chemistry conversions. Herein, we have covered all known supported-coupling reagents and bases which have had a great impact in amide/peptide bond formation. These coupling reagents have been used for the activation of a carboxyl moiety; thus generating an active acylating species that is ready to couple with an amine nucleophile liberating the amide/peptide and polymeric support which can be regenerated for reuse. This also addresses a large variety of anchored coupling reagents, additives, and bases that have only been employed in amide/peptide syntheses during the last six decades.
Amides are an essential group of organic compounds with a wide range of potential uses in both commercial and academic arenas. Many of these compounds also have biological and medicinal activities. Because of this, they have drawn interest as one of the principal topics of study in organic chemistry. The study of amide compounds has become more common over the last few years. So many synthetic techniques to produce amide bonds have been proposed as a result. Transamidation, which involves direct amide-to-amide conversion, is becoming more and more well-liked as a superior method for generating a variety of amides without the need for acid-amine coupling or other intermediate steps. In addition to synthetic organic chemistry, amides have also been studied in other areas such as chemical biology and polymer science. In this review, we briefly explain the recent accomplishments in the field of transamidation.
Imines in Stille-Type Cross-Coupling Reactions: A Multicomponent Synthesis of a-Substituted Amides
Cheminform, 2004
Palladium-catalyzed cross-coupling processes such as the Stille reaction have emerged as some of the more important methods for the construction of carbon-carbon bonds. [1] A useful feature of the Stille coupling is its use of nonpolar organostannanes, rather than nucleophilic agents, in reactions with organic halides. Organotin reagents are generally airand moisture-stable, and they can be prepared with a diverse range of transferrable substituents, many of which are less readily formed, or unavailable, within nucleophilic reagents [*] J.
Coupling of amides with ketones via C-N/C-H bond cleavage: a mild synthesis of 1,3-diketones
Chen, J.; Xia, Y.; Lee, S. Org. Chem. Front. 2020, 7(19), 2931-2937, 2020
A variety of aryl and alkyl-substituted tertiary amides react with ketones in the presence of LiHMDS and a variety of primary and secondary amides in one pot to give the corresponding 1,3-diketone products in good to excellent yields via C-N cleavage of amides and deprotonation of ketones. The reaction was conducted at room temperature under transition-metal-free conditions. N-Tosyl-, N-triflyl-, N-mesyl-, and N-Boc-substituted tertiary amides including N-benzoyl saccharin and N-benzoyl succinimide showed good activity in the reaction. The broad scope, good functional group tolerance of substrates and gram-scale synthesis showed the great importance and potential of this protocol in organic synthesis and industrial manufacture. Scheme 1 C-N cleavage of amides. † Electronic supplementary information (ESI) available. See
Imines in Stille-Type Cross-Coupling Reactions: A Multicomponent Synthesis ofα-Substituted Amides
Angewandte Chemie International Edition, 2004
Palladium-catalyzed cross-coupling processes such as the Stille reaction have emerged as some of the more important methods for the construction of carbon-carbon bonds. [1] A useful feature of the Stille coupling is its use of nonpolar organostannanes, rather than nucleophilic agents, in reactions with organic halides. Organotin reagents are generally airand moisture-stable, and they can be prepared with a diverse range of transferrable substituents, many of which are less readily formed, or unavailable, within nucleophilic reagents [*] J.
Synthesis and biological importance of amide analogues
2018
The present research article deals with the amide analogues prepared by available very well-known name reactions. The author have studied the name reactions like Beckmann rearrangement, Schmidt reaction, Passerine reaction, Willgerodt–Kindler reaction and UGI reaction, which involves preparation of amide linage containing compounds. The main purpose of article is to provide information on the development of novel amide derivatives to the scientific community. Doing so, it focuses on mechanisms of action and adverse events, and suggests measures to be implemented in the clinical practice according to bioethical principles.
N,N-Dialkyl Amides as Versatile Synthons for Synthesis of Heterocycles and Acyclic Systems
Organic Synthesis - A Nascent Relook [Working Title]
N,N-Dialkyl amides such as N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), are common polar solvents, finds application as a multipurpose reagent in synthetic organic chemistry. They are cheap, readily available and versatile synthons that can be used in a variety of ways to generate different functional groups. In recent years, many publications showcasing, excellent and useful applications of N,N-dialkyl amides in amination (R-NMe 2), formylation (R-CHO), as a single carbon source (R-C), methylene group (R-CH 2), cyanation (R-CN), amidoalkylation (-R), aminocarbonylation (R-CONMe 2), carbonylation (R-CO) and heterocycle synthesis appeared. This chapter highlights important developments in the employment of N,N-dialkyl amides in the synthesis of heterocycles and functionalization of acyclic systems. Although some review articles covered the application of DMF and/or DMA in organic functional group transformations, there is no specialized review on their application in the synthesis of cyclic and acyclic systems.
Chemical Communications, 2015
Reagents and Materials. General 1 H NMR were recorded at 298 K, unless otherwise stated, on a Bruker AVANCE 300 spectrometer operating at 300.15 MHz. δ values in ppm are relative to SiMe4. GC analysis were performed on HP SERIES II 5890 equipped with a HP5 column (30 m, I. D. 0.25 m, film 0.25 μm) using He as gas carrier and FID. GC-MS analyses were performed on a GC Trace GC 2000 equipped with a HP5-MS column (30 m, I.D. 0.25 mm, film 0.25 m) using He gas carrier and coupled with a quadrupole MS Thermo Finnigan Trace MS with Full Scan method. Solvents and reactants were used as received; otherwise they were purified as reported in the literature. 1 TLC analysis were performed on TLC Polygram ® Sil G/UV254 of 0.25 mm thickness and flash-chromatography separations were performed on silica gel Merk 60, 230-400 mesh. 2 Substrates and capsule All carboxylic acids 3 and amines 4 as well as the coupling agent 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride 2 are all commercially available products (Aldrich) and were used as received without any further purification. Resorcin[4]arene 1 was prepared as reported in the literature. 3 Amide products 5 were determined by GC-MS analysis. Catalytic Studies Catalytic reactions of amide coupling between acids 3 with amines 4 mediated by the carbodiimide 2 in the presence of the capsule 1 6 •8H 2 O Water saturated solvent was prepared by shaking chloroform-d with bidistilled water at room temperature in a separation funnel. Resorcin[4]arene 1 (6.6 equivalents, 81.4 mM) was placed in a screw-capped vial equipped with silicone septum and dissolved in the water saturated chloroform-d (1 mL) stirring for few minutes. To this solution, 1-ethyl-3-(-3dimethylaminopropyl) carbodiimide hydrochloride 2 (1 equivalent, 13.2 mM) was added, followed after few minutes stirring, by octane, decane, dodecane, tetradecane, or docosane as GC-MS standard (3.3 mM), a series of carboxylic acids (0.5 equivalents each, 6.7 mM) and a series of amines (0.5 equivalents each, 6.7 mM). The reaction was then left at 60°C under vigorous stirring for 2 days and the reaction progress was monitored by GC-MS analysis by periodically sampling directly from the reaction mixtures. Conversion, product assignment and distribution were determined by direct GC-MS analysis of the reaction mixture as the average of three experiments. GC-MS analyses were performed on a GC Trace GC 2000 coupled with a quadrupole MS Thermo Finnigan Trace MS with Full Scan method. Experimental conditions are reported in the following table.