Acyl group vs nitrogen protonation of carboxylic and �non-carboxylic amides in the gas phase and water

7 Reaction mechanisms. Part (i) Polar reactions

“…138 At the concentrations of reactants used in alkylation reactions the dimeric form of enolate was the most abundant, but the monomeric enolate was found to be the most reactive towards alkylation. Experimental and theoretical 13 C and 17 O kinetic isotope effects were determined for the chlorotrimethylsilane mediated addition of lithium dibutylcuprate to cyclohexenone in THF. 139 These results were consistent with rate-limiting silylation of an intermediate p-complex of enone and cuprate in the overall addition mechanism.…”

“…16 The site of protonation of carboxylic and non-carboxylic amides in the gas phase and in water was analyzed by heteronuclear NMR spectroscopy and quantum chemical calculations. 17 NMR techniques were also used to demonstrate that protonation of substituted 3-aminoindoles only occurred at the ring nitrogen, whereas protonation of 2-aminoindoles also occurred at the 2-amino substituent depending on the nature of the Scheme 1 3-substituent. 18 The kinetic site of protonation of CpW(CO) 2 (PMe 3 )H was shown to be the hydride ligand rather than the metal by measurements of exchange rates with various acids and a value of pK a = 5.6 determined for CpW(CO) 2 (PMe 3 )(H 2 ) + .…”

Determination of protonation constants and structural correlations for some tertiary formamides and acetamides in sulfuric acid with UV spectroscopy

“…Many authors have agreed that the O-atom from the carbonyl group, compared to the N-atom from the amide group, is the predominant protonation site, but there are a few other opinions as well [17,18]. In the recent investigations, employing quantum chemical calculations and heteronuclear NMR measurements of carboxylic and non-carboxylic amides, Bagno et al [25] have concluded that, generally (with few exceptions, e.g. sulfonamides, sulfinamides and sulfenamides), amides are protonated on the acid residue.…”

10.1007/s11178-008-1006-y

“…In the recent years, considerable progress was achieved in the calculations of acidity parameters (such as proton affinity ΔH H and basicity ΔG) of molecules of many organic compounds in the gas phase [21,[25][26][27][28][29]. Therefore, it became possible to draw reliable relations between ΔH H and structural parameters [31][32][33]36] or other properties [27,28,[30][31][32][33][34][35][36][37] and describe competing protonation processes involving multicenter molecules [27,28,34,35] and gas-phase tautomeric protontransfer equilibria [34,37]. In the past 5 years, the error in the calculation of the above acidity parameters for the gas phase was smaller than 1% [25,30,41,44].…”