Site of Protonation of Carboxylic and Non-Carboxylic Amides in the Gas Phase and in Water

Abstract

The site of protonation of several types of amide bases (carboxylic amides and thioamides, sulfenamides, sulfinamides, sulfonamides, nitrosamides, nitramides, cyanamides, and phosphorous and phosphoric acid triamides) has been investigated through a combination of quantum chemical calculations and heteronuclear NMR measurements. Relative energies of tautomeric ions deriving from protonation at the various sites were determined both in the gas phase (by MP2 calculations) and in water (by the IPCM continuum solvation method). Relevant NMR properties of the involved heteronuclei (nuclear shielding and electric field gradient) were calculated at the GIAO-HF level, and compared with chemical shifts and relaxation rates experimentally measured in 14 N, 17 O, and 31 P spectra. It is shown that such a combination of theoretical and experimental tools allows a dependable prediction of spectral parameters and ultimately of the protonation site of amides. The reliability of common assumptions, like the comparison of spectral parameters of polyfunctional bases and monofunctional models, is also scrutinized and tested.

Aplicação da química quântica computacional no estudo de processos químicos envolvidos em espectrometria de massas

“…Entretanto, quando os grupos funcionais são parecidos, tal como os nitrogênios de cadeia lateral e de anel de histamina ou pirimidinas, a identificação do sítio mais básico não é obvia. 7,8 Mesmo em casos aparentemente simples, como o de uma amida carboxílica, com apenas dois possíveis sítios de protonação (O e N), o sítio mais básico não pode ser predito a partir de argumentos simples, 9 embora isto seja erroneamente feito com freqüên-cia, uma vez que a ressonância entre o par de elétrons do nitrogê-nio e a carbonila do grupo amida resulta em um comportamento muito diferente daquele observado para grupos funcionais semelhantes, tais como aminas e cetonas.…”

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

“…1 We showed previously 4-7 that a powerful means to solve this problem is the analysis of the changes in the NMR longitudinal relaxation times (T 1 ) of all nuclei which can act as ionization sites, coupled with suitable quantum chemical calculations. [4][5][6][7][8][9] In this paper we review the scope of this approach, including the calculation of nuclear shieldings, and also the relative stabilities, of all ionic species than can conceivably be formed from protonation at each basic site. Structures, energies and electric field gradients (efg) were calculated at the MP2/6-31G(d,p)//HF/6-31G(d,p) and MP2/6-311G(d,p)//HF/6-311G(d,p) levels.…”

“…Structures, energies and electric field gradients (efg) were calculated at the MP2/6-31G(d,p)//HF/6-31G(d,p) and MP2/6-311G(d,p)//HF/6-311G(d,p) levels. [4][5][6][7][8][9] Nuclear shielding calculations were carried out with the GIAO-HF method. 10,11 Moreover, since solvent effects will affect the relative stability of ions, energies in water were calculated with the HF-IPCM continuum solvent method.…”

“…12 Subsequently we shall compare the relative energies of the possible ionic species in the gas phase (DE g , determined from MP2 calculations) and in water (DE aq , calculated through a combination of MP2 and IPCM energies by means of a Born-Haber cycle). 4 The comparison of calculated and experimental NMR properties is presented as follows. The relaxation time of quadrupolar nuclei such as 14 N and 17 O is proportional to the effective nuclear quadrupolar coupling constant w eff = w 2 (1 Z 2 /3), where w and Z depend on the efg at the nucleus in question, so that 1/T 1 G w eff .…”

“…The relaxation time of quadrupolar nuclei such as 14 N and 17 O is proportional to the effective nuclear quadrupolar coupling constant w eff = w 2 (1 Z 2 /3), where w and Z depend on the efg at the nucleus in question, so that 1/T 1 G w eff . 4 We then compare the calculated values of w eff (BH )/w eff (B) with the experimental counterpart T 1 (B)/T 1 (BH ). Hence a decrease in T 1 (i.e.…”