Protonation of amides

Protonation of carbonyl oxygen Protonation of amide nitrogen... 

The chemical shift of the N—H proton of amides appears m the range 8 5-8 It IS often a very broad peak sometimes it is so broad that it does not rise much over the baseline and can be lost m the background noise... 

Further evidence for nitrogen as the site of protonation of amides in largely aqueous acid comes from studies of substituent effects on the p/Sfa Value of benzamide (Edward et al., 1960 Yates and Stevens, 1965). It has been observed that the pi g-values are correlated with a-constants of the substituents, rather than with o. This means that the structure of the dominant form of the cation is N-protonated as in [112], because resonance interactions of para-substituents in this kind of cation are similar to those in benzoic acid. The p-value (0 92)... 

Several lines of kinetic evidence have also to be considered in connection with the site of protonation of amides. Salts of the type [119] (R = Me or Ph) have been prepared by Klages cind Zange... 

The proton nmr resonances of the N—H protons of amides are different from any we have discussed so far. Generally, these will appear at room temperature as a broad singlet absorption, which may turn into a broad triplet at higher temperatures. A typical example is propanamide (Figure 24-2). 

The protonation of amides (A) to yield the conjugated acids (AH+) in aqueous sulphuric acid takes place on the carbonyl oxygen158-161 and the ionization ratio (I = [AH+]/[A]) has been found to depend on the acidity of the solution as measured by the Ha acidity function25,162 163 where A ah+ is the thermodynamic dissociation constant of the conjugated acid (equations 33 and 34). 

Several new catalytic asymmetric protonations of metal enolates under basic conditions have been published to date. In those processes, reactive metal enolates such as lithium enolates are usually protonated by a catalytic amount of chiral proton source and a stoichiometric amount of achiral proton source. Vedejs et al. reported a catalytic enantioselective protonation of amide enolates [35]. For example, when lithium enolate 43, generated from racemic amide 42 and s-BuLi, was treated with 0.1 equivalents of chiral aniline 31 followed by slow addition of 2 equivalents of ferf-butyl phenylacetate, (K)-enriched amide 42 was obtained with 94% ee (Scheme 2). In this reaction, various achiral acids were... 

Most double resonance measurements of proton shifts have been homonuclear studies of hidden and unresolved lines (e.g. refs. 107 and 366). However, in NMR, measurements of proton shifts using the correlation of C and spectra by off-resonance decoupling is common. While the aim is usually to assign the signals, it can also be to assign proton signals, as in the case of the N-methylene protons of amides (367) and the methyl signals of valine. (368) H shifts derived from similar experiments can be used as trial parameters for the iterative analysis of complex H spectra this technique was demonstrated for [l,l,3- H3]indene. (369)... 

The acidic initiator increases the reactivity of the lactam carbonyl towards nucleophiles. Although protonation of amides occurs preferentially at the oxygen atom [47] a small amount of A-protonated lactam is assumed to be present in the tautomeric equilibrium [178—181]... 

Nmr. Absorption by N—H protons of amines falls in the range B 1-5, where it is often detected only by proton counting. Absorption by —CO—NH— protons of amides (Sec. 20.25) appears as a broad, low hump farther downfield (8 5-8). 

The question of the site of protonation of amides in strongly acidic media has been thoroughly investigated by means of the proton spectra of 15N-acetamide at various temperatures and acid concentrations. (149) The coupling pattern is consistent with the presence of a large excess of the O-protonated form [77], in anhydrous H2S04 and HS03F, in... 

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