Hydrolysis and carbonyl-oxygen exchange in tertiary amides. Estimation of the free energy changes for breakdown and conformational changes of tetrahedral intermediates

Deslongchamps, Pierre; Barlet, R.; Taillefer, Roland J.

doi:10.1139/v80-347

Cited by 16 publications

(12 citation statements)

References 8 publications

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“…The mechanism of the alkaline amide hydrolysis has been intensively investigated. [14][15][16][17][18][19][20][21] It is similar to that of the esters, with the exception that the tetrahedral intermediate, formed after the addition of the hydroxide, could regenerate the amide than give the hydrolysis products. The loss of the hydroxide anion is the thermodynamically preferred route and the accompanying oxygen exchange is generally faster than hydrolysis (Scheme 1).…”

Section: Introductionmentioning

confidence: 72%

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A mild alkaline hydrolysis of N- and N,N-substituted amides and nitriles

Théodorou¹,

Paraskevopoulos²,

Skobridis³

2015

Arkivoc

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A mild protocol for the alkaline hydrolysis of secondary and tertiary amides in non-aqueous conditions, by the use of NaOH in methanol/dichloromethane or methanol/dioxane (1:9) at room temperature or under reflux, has been developed and a plausible reaction mechanism is discussed. Primary amides are hydrolyzed much slower than with the classical procedure, while nitriles are converted selectively to primary amides.

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Section: Introductionmentioning

confidence: 72%

“…With our methodology, nitriles (14)(15)(16)(17) are readily hydrolyzed to amides, but very slowly to the corresponding acid salts. This means that our method may allow the selective hydrolysis of a nitrile to primary amide.…”

Section: Resultsmentioning

confidence: 99%

A mild alkaline hydrolysis of N- and N,N-substituted amides and nitriles

Théodorou¹,

Paraskevopoulos²,

Skobridis³

2015

Arkivoc

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“…68 However, I also knew that there was no evidence for it, although we detected it in the reactions of some hydroxylamines, where it is fairly slow, with a second-order rate constant k 2 near 10 4 M -1 s -1 . 69 What puzzled me was the reason for postulating such a mechanism.…”

Section: Another Mechanism For Nh Exchangementioning

confidence: 80%

The Logic behind a Physical–Organic Chemist’s Research Topics

Perrin

2016

J. Org. Chem.

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Abstract. Although my research has no common theme or defining area, a coherence connects the diverse topics, insofar as one project leads logically to another. Thus studies on mechanisms of hydrogen exchange in amides and amidines led to the influence of hydrogenbonding and to NMR methods for chemical kinetics, including 2D-EXSY spectroscopy.Another connection was the OH --catalyzed NH exchange in amines that had supported the hypothesis of stereoelectronic control. We therefore analyzed that hypothesis critically, tested it, found counterexamples, and proposed an alternative hypothesis. We next addressed one-bond NMR coupling constants in ethers and the reverse anomeric effect. The latter studies required a highly accurate NMR titration method that we developed to measure the additional steric bulk resulting from protonation of a substituent. This method is also applicable to measuring secondary isotope effects on acidity, and we could demonstrate that they arise from n-* delocalization, not from an inductive effect. Other studies included kinetic isotope effects for both dissociation and H exchange of aqueous NH 4 + , for C-N rotation in amides, and for a hydride transfer. The role of hydrogen-bonding led us to the rotation of NH 4 + within its solvent cage and then to the symmetry of hydrogen bonds. This review article is based on an address presented at the 249th National Meeting of the American Chemical Society in Denver CO, on the occasion of the James Flack Norris Award in Physical-Organic Chemistry. 1 It demonstrates the ways whereby one physicalorganic chemist, and physical-organic chemists in general, have investigated how molecular structure affects chemical reactivity. It also seeks to confirm my claim that "In my opinion, 2 physical organic chemistry represents the intellectual basis of organic chemistry. It asks (and answers!) fundamental questions about how chemical substances behave, and it rationalizes that behavior." 2 The reason that I won the James Flack Norris Award was for my "insight, rigorous analysis, and understanding of mechanisms and reactive intermediates", rather than any distinctive area of research with which I am associated. Instead of choosing one area to review here, I have tried to describe the path of my research for the past 40 years, as an expansion of an earlier article on this topic. 3 Each area seems to have engendered additional questions, leading to additional areas. Often those questions are marked by an intense skepticism, and the answers to those questions are supported by a logical analysis that I am proud of. I hope that this article will be as interesting, informative, and enjoyable to the reader as the research described here has been for me. A Beginner's ResearchMy Ph.D. thesis research was on mercuration of benzene, an electrophilic aromatic substitution that is accelerated by strong acid, and where we measured the H/D kinetic isotope effect. 4 To understand the origin of the acceleration it was necessary to consider acidity functions, including a new one, H...

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“…The formation of the tetrahedral intermediate is in most cases the rate‐determining step of the reaction. However, though the addition–elimination mechanism is believed to operate in most carboxylic derivative reactions, there are several examples where the occurrence of a dianionic intermediate is proposed to explain a parabolic dependence of rate constant upon hydroxide concentration, as it happens with activated carbonyl compounds such as acetanilides,12–27 formanilides,23, 28–30 acetamides,31, 32 lactams,23, 33–35 acylpyrroles,36 ureas,37, 38 phthalamic acids,39 phthalamides40 or beta‐sultams 41…”

Section: Introductionmentioning

confidence: 99%

Basic hydrolysis of quinolinyl N,N‐dimethylcarbamates: a two‐step mechanism

Silva

Norberto

Santos

et al. 2011

J of Physical Organic Chem

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The reactivity of 6-quinolinyl and 8-quinolinyl N,N-dimethylcarbamates was examined in several aqueous basic media. A quadratic dependence was observed for the constant rates upon hydroxide concentration for both compounds, which is a typical behaviour of a mechanism involving a base-catalysed deprotonation of the tetrahedral intermediate with the formation of a dianion at high concentrations of hydroxide ion, while at lower concentrations a specific-base catalysed addition-elimination mechanism seems to be predominant. The reactivity of 8-quinolinyl N,N-dimethylcarbamate was also studied in several amine buffers, showing specific base catalysis. The reactivity of 6-quinolinyl N,N-dimethylcarbamate was studied in H 2 O and in D 2 O and the solvent isotope effect supports the proposal of a mechanism involving a specific-base hydrolysis. All results confirm the existence of a mechanism with a rate determining step involving the substrate anion and a second mole of hydroxide ion. This mechanism was so far unknown for carbamate reactivity, being only known to occur with amides. In the present study, the hydrolysis 8-quinolinyl and 6-quinolinyl N,N-dimethylcarbamates (compounds 1 and 2, respectively) were studied in several basic media, and a similar behaviour to the one showed by activated anilides was observed, in which kinetic constants show a quadratic dependence on hydroxide concentration.(wileyonlinelibrary.com)

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Hydrolysis and carbonyl-oxygen exchange in tertiary amides. Estimation of the free energy changes for breakdown and conformational changes of tetrahedral intermediates

Abstract: . Can. J. Chem. 58,2167Chem. 58, (1980. Second order rate constants were measured at several temperatures for the basic hydrolysis and for concurrent carbonyl

Cited by 16 publications

References 8 publications

A mild alkaline hydrolysis of N- and N,N-substituted amides and nitriles

A mild alkaline hydrolysis of N- and N,N-substituted amides and nitriles

The Logic behind a Physical–Organic Chemist’s Research Topics

Basic hydrolysis of quinolinyl N,N‐dimethylcarbamates: a two‐step mechanism

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