Direct amide formation from unactivated carboxylic acids and amines

Allen, C. M. Van; Chhatwal, A. Rosie; Williams, Jonathan M. J.

doi:10.1039/c1cc15210f

Cited by 309 publications

(178 citation statements)

References 28 publications

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“…11 Recently, it was shown that a significant amount of the 15 amide product can be formed even at lower temperatures, usually with azeotropic removal of water. 12,13,14 The yields of the thermal amidation reaction is highly substrate dependent, as well as dependent on temperature, substrate concentration, solvent and other reaction parameters. As an example, the thermal yield of N-20 (4-methylbenzyl)-3-phenylpropanamide at 110 ºC under neat conditions was reported to be 58%, whereas the same product was formed quantitatively in toluene at 2 M concentration with the same reaction time and temperature (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

“…As an example, the thermal yield of N-20 (4-methylbenzyl)-3-phenylpropanamide at 110 ºC under neat conditions was reported to be 58%, whereas the same product was formed quantitatively in toluene at 2 M concentration with the same reaction time and temperature (Scheme 1). 13 For comparison, the structurally similar N-benzylphenylacetamide 25 was formed in only 13% yield or less, when phenylacetic acid and benzylamine were allowed to react in THF at 70 ºC at a concentration of 0.4 M and a reaction time of 24 hours. 15 The literature on thermal amidation is not covered in this review unless the non-catalysed reaction is specifically mentioned by the 30 authors.…”

Section: Introductionmentioning

confidence: 99%

“…13 In the reaction of 3-55 phenylpropionic acid and 4-methylbenzylamine, the corresponding amide was formed in 20% yield after 4 hours, and a full conversion was obtained after 20 hours in the absence of a catalyst. However, the authors found that the reaction rate was dramatically increased by the addition of various metal 60 complexes in catalytic amounts.…”

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Catalytic amide formation from non-activated carboxylic acids and amines

et al. 2014

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The amide functionality is found in a wide variety of biological and synthetic structures such as proteins, polymers, pesticides and pharmaceuticals. Due to the fact that synthetic amides are still mainly produced by the aid of coupling reagents with poor atom-economy, the direct catalytic formation of amides from carboxylic acids and amines has become a field of emerging importance. A general, efficient and selective catalytic method for this transformation would meet well with the increasing criterias for green 10 chemistry. This review covers catalytic and synthetically relevant methods for direct condensation of carboxylic acids and amines. A comprehensive overview of homogeneous and heterogeneous catalytic methods is presented, covering biocatalysis, Lewis acid catalysts based on boron and metals as well an assortment of other types of catalysts.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Catalytic amide formation from non-activated carboxylic acids and amines

et al. 2014

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“…These derivatives were associated with broad spectrum of biological activities including antituberculosis, 25 …”

Section: 23mentioning

confidence: 99%

Synthesis, Characterization and Antimicrobial Activity of Bifunctional Sulfonamide-Amide Derivatives

Abbavaram¹,

Reddyvari²

2013

Journal of the Korean Chemical Society

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ABSTRACT. A convenient synthesis of bifunctional sulfonamide-amide derivatives was reported. Amide coupling of 4-methyl benzoic acid 1 followed by reaction with chlorosulfonic acid produce ethyl-4-(3-(chlorosulfonyl)-4-methylbenzoyl)piperazine-1-carboxylate 4. The resulted compound on further treatment with various anilines produces the title sulfonamide-amide derivatives 5a−n. The configurations of these compounds were established by elemental analysis, IR, 1 H NMR, mass spectra, and by their preparation from the corresponding 4-methyl benzoic acid 1 and chlorosulfonic acid. All these new compounds demonstrate significant in vitro antibacterial and antifungal activities against all bacterial and fungal strains.

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“…A novel amide-bond forming method recently published by Allen et al was adopted to form the desired amides without the requirement for extensive purification. [193] The acid and the amine were refluxed in toluene overnight with a ZrCp 2 Cl 2 Lewis acid catalyst to yield, in most cases, the desired amide as the only product in 100 % conversion.…”

Section: Scheme 25mentioning

confidence: 99%

Kinetic Template‐Guided Tethering of Fragments

2012

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This thesis is composed of two separate projects: Kinetic Template-Guided Tethering of Fragments and Design and Synthesis of a Chemical Probe to Dissect the Cellular Signalling Cascade leading to Cyclin D1 Degradation after DNA Damage. Kinetic Template-Guided Tethering of FragmentsThe development of a novel methodology for the site-directed discovery of small molecule, protein-binding ligands is described. The protein of interest, with a cysteine thiol (either native or engineered) adjacent to the desired binding pocket, is incubated with mixtures of low molecular weight compounds (fragments) modified with either an acrylamide or a vinyl sulfonamide capture group. Any ligand within the mixture that binds within the pocket brings the capture group into close proximity with the cysteine thiol, promoting a conjugate addition reaction at an increased rate over the background reaction. The capture reaction is designed to be slow, such that during the time course of an experiment, no adduct formation is observed unless the reaction is templated by the protein. By this method, binding ligands are rapidly identified by mass spectrometry analysis of the crude reaction mixtures. The methodology has been termed 'kinetic template-guided tethering'. Design and Synthesis of a Chemical Probe to Dissect the Cellular Signalling Cascade leading to Cyclin D1Degradation after DNA Damage An inhibitor described within the literature was found to attenuate the reduction of cyclin D1 after DNA damage to cells. In order to implement a two-step chemical proteomics strategy to find the molecular target of this inhibitor, a synthesis of the compound with an alkyne appendage was required. The alkyne acts as a functional handle for attachment of a reporter molecule in cells via the Huisgen cycloaddition ('Click') reaction. The design and synthesis of this inhibitor with the alkyne appendage is described.

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Direct amide formation from unactivated carboxylic acids and amines

Abstract: The direct coupling of unactivated carboxylic acids with amines can be performed in toluene 110 °C in the absence of catalyst. The use of simple zirconium catalysts at 5 mol% loading gave amide formation in as little as 4 h.

Cited by 309 publications

References 28 publications

Catalytic amide formation from non-activated carboxylic acids and amines

Catalytic amide formation from non-activated carboxylic acids and amines

Synthesis, Characterization and Antimicrobial Activity of Bifunctional Sulfonamide-Amide Derivatives

Kinetic Template‐Guided Tethering of Fragments

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