Direct synthesis of amides from nonactivated carboxylic acids using urea as nitrogen source and Mg(NO<sub>3</sub>)<sub>2</sub>or imidazole as catalysts

Chhatwal, A. Rosie; Lomax, Helen; Blacker, A. John; Williams, Jonathan M. J.; Marcé, Patricia

doi:10.1039/d0sc01317j

Cited by 34 publications

(24 citation statements)

References 117 publications

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“…[30]). Primary amide bond forming methods, as recently reported, [31] will also not be covered as they are of limited interest with regards to peptide synthesis. While biocatalyic amidation is outside the scope of this review due length constraints and the choice to focus on synthetic methods, this approach offers some potential advantages when compared with the works that will be discussed herein.…”

Section: Alternative Approaches To Noncanonical Amidationmentioning

confidence: 99%

Recent developments in catalytic amide bond formation

Todorovic

Perrin

2020

Peptide Science

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Amide bond forming reactions are critical for both polypeptide synthesis and medicinal chemistry. Most current approaches for amidation employ stoichiometric activating agents, but such methods are neither atom economical nor synthetically elegant. Catalytic approaches for amidation are potentially green and more ideal substitutes for current standard methods and thus are the subject of this review. Such methods face significant thermodynamic and kinetic barriers and have, as a result, historically

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Section: Alternative Approaches To Noncanonical Amidationmentioning

confidence: 99%

Recent developments in catalytic amide bond formation

Todorovic

Perrin

2020

Peptide Science

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“…The title compound was synthesized following the reported procedure as colorless crystals (840 mg, 98%) …”

Section: Methodsmentioning

confidence: 99%

“…It is evident that Lewis and Brønsted acids are required to mitigate the high stability of amide bonds. In traditional primary amide synthesis, carboxylate salts of ammonia or urea (RCO 2 ·NH 4 or RCO 2 H·urea) undergo a dehydrative addition/elimination reaction without any additives at high reaction temperatures. , This reaction generates CO 2 and ammonia as byproducts, which can form ammonium salts in the presence of water. However, it is unclear whether such byproducts and adducts (CO 2 , ammonia, ammonium carbonate, and bicarbonate) have influences in the amide bond formation reaction.…”

Section: Introductionmentioning

confidence: 99%

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A CO₂-Catalyzed Transamidation Reaction

et al. 2021

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Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Here we report the use of CO 2 as a traceless catalyst: in the presence of catalytic amounts of CO 2 , transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular, N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO 2 -catalyzed transamidation versus a N 2 atmosphere. Comparative Hammett studies and kinetic analysis were conducted to elucidate the catalytic activation mechanism of molecular CO 2 , which was supported by DFT calculations. We attributed the positive effect of CO 2 in the transamidation reaction to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO 2 .

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“…Amide bond is a crucial functional group, which is ubiquitous in many important compounds, such as proteins, drugs, fertilizers, and plastics. Traditionally, amides are mainly prepared by amidation reactions of a range of starting materials including carboxylic acid derivatives, − aldehydes, − and alcohols. − Another two common methods for the synthesis of amides involve the hydrolysis of nitriles − and rearrangement of oxime. − Because of the broad applications of amides in both industrial and medicinal chemistry, the development of versatile methods for preparing amides is still an attractive research field.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Titanium Complexes Supported by Carbinolamide- and Amide-Containing Ligands Derived from Ti(NMe₂)₄-Mediated Selective Amidations of Carbonyl Groups

et al. 2020

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An efficient strategy for the syntheses of a series of titanium complexes has been developed. This protocol features the employment of Ti(NMe 2 ) 4 both as the metal center to trigger the deprotonation of the ligands and as an amine source to proceed the amidation reactions of carbonyl functionalities of the ligands. Treatment of Ti(NMe 2 ) 4 with a ligand HL1 (HL1 = 2,2′-(((2hydroxybenzyl)azanediyl)bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) results in the formation of Ti(L1′)(NMe 2 ) (1) (H 3 L1′ = N1-(2-((2-(1-(dimethylamino)-1-hydroxy-3-oxoisoindolin-2-yl)ethyl)(2-hydroxybenzyl)amino)ethyl)-N2,N2-dimethylphthalamide). One important feature regarding the synthesis of 1 is the occurrence of the in situ metal−ligand reaction between Ti(NMe 2 ) 4 and HL1, leading to the simultaneous formations of carbinolamide and amide scaffolds. Another prominent feature in terms of the preparation of 1 is the achievement of the selective ring-opening reaction of one of the two phthalimide units of the HL1 ligand, affording carbinolamide and amide functionalities within one ligand set. The developed methodology characterizes an ample substrate scope. The selective amidation reactions of the carbonyl groups have been realized for a series of analogous ligands HL2− HL7. Density functional theory calculations were employed to disclose the mechanisms for the formation of 1−7, and the details for the selective ring-opening reactions of the phthalimide unit were uncovered.

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Direct synthesis of amides from nonactivated carboxylic acids using urea as nitrogen source and Mg(NO₃)₂or imidazole as catalysts

Abstract: This methodology is particularly useful for the direct synthesis of primary and N-methyl amides using urea as a stable and easy to manipulate nitrogen source.

Cited by 34 publications

References 117 publications

Recent developments in catalytic amide bond formation

Recent developments in catalytic amide bond formation

A CO₂-Catalyzed Transamidation Reaction

Synthesis of Titanium Complexes Supported by Carbinolamide- and Amide-Containing Ligands Derived from Ti(NMe₂)₄-Mediated Selective Amidations of Carbonyl Groups

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Direct synthesis of amides from nonactivated carboxylic acids using urea as nitrogen source and Mg(NO3)2or imidazole as catalysts

Abstract: This methodology is particularly useful for the direct synthesis of primary and N-methyl amides using urea as a stable and easy to manipulate nitrogen source.

Cited by 34 publications

References 117 publications

Recent developments in catalytic amide bond formation

Recent developments in catalytic amide bond formation

A CO2-Catalyzed Transamidation Reaction

Synthesis of Titanium Complexes Supported by Carbinolamide- and Amide-Containing Ligands Derived from Ti(NMe2)4-Mediated Selective Amidations of Carbonyl Groups

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Product

Resources

About

Direct synthesis of amides from nonactivated carboxylic acids using urea as nitrogen source and Mg(NO₃)₂or imidazole as catalysts

A CO₂-Catalyzed Transamidation Reaction

Synthesis of Titanium Complexes Supported by Carbinolamide- and Amide-Containing Ligands Derived from Ti(NMe₂)₄-Mediated Selective Amidations of Carbonyl Groups