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Imidazo[1,2-a]pyrazine-3,6-diones are unusual compounds composed of three alpha-amino acid fragments. These bicyclic amidines (BCAs) form under high temperatures or with the use of strong dehydrating reagents. We gave insight into the mechanisms of BCA formation via gas-phase pyrolytic and silica-catalyzed reactions of glycine (Gly) and alpha-aminoisobutyric acid (AIB) with related diketopiperazines (DKPs), using quantum chemical calculations. The entire process requires four steps: (1) O-acylation of DKP with free or silica-bonded amino acid, (2) acyl transfer from the oxygen to the nitrogen atom, (3) intramolecular condensation of the N-acyl DKP into a cyclol, and (4) elimination of water. To study step (1) at silica surface (modeled by H7Si8O12-OH cluster), we employed two-level ONIOM calculations (AM1:UFF, B3LYP/3-21G:UFF and B3LYP/6-31G(d):UFF); all gas-phase reactions were studied at the AM1, B3LYP/3-21G and B3LYP/6-31G(d) levels. The catalytic effect of silica was observed for both Gly and AIB: the activation energy in the O-acylation at the surface was lower by more than 9 kcal mol(-1) as compared to the gas-phase process. Contrary to the exothermic O-acylation, the gas-phase transfer reaction (step 2) was exothermic in both cases, but more favorable for Gly. The cyclocondensation of N-acylated DKPs into BCAs (steps 3 and 4) is endothermic for Gly and exothermic for AIB.

Imidazo[1,2-a]pyrazine-3,6-diones and imidazo[1,2-a]imidazo[1,2-d]pyrazine-3,8-diones can be produced by pyrolysis of simple amino acids. While such bicyclic and tricyclic amidines were detected and characterized by IR spectroscopy for some alpha-substituted amino acids, the parent systems composed of glycine fragments are unknown up to now. IR spectra for five amidines derived from glycine were calculated by using different semi-empirical (PM3, AM1, MNDO and MINDO/3), HF, and hybrid DFT (B3LYP, B3P86 and B3PW91) methods in conjunction with 6-31G(d) basis set (for HF and DFT). Vibration frequencies in the experimental IR spectra were predicted based upon the B3LYP data, by correcting the calculated wavenumbers by a scaling factor of 0.959. The behavior of most characteristic bands (nu(CX), nu(NH), etc.) and their shifts with respect to such bands in the spectra of alanine and alpha-aminoisobutyric acid derivatives studied before, are discussed. Performance of the semi-empirical methods was tested, bearing in mind possible future needs for IR spectra predictions for larger molecular systems of similar chemical nature; the use of MINDO/3 and MNDO is recommended. A basis set effect on the B3LYP fundamental vibration frequencies for hexahydroimidazo[1,2-a]pyrazine-3,6-dione was studied by varying Pople basis sets from minimal STO-3G to 6-311++G(d, p). No significant improvements were found beyond the 6-31G(d) basis set, which thus can be recommended to predict IR spectra for the amidines and similar molecules.