Imidazo[1,2-a]pyrazine-3,6-diones derived from alpha-amino acids: a theoretical mechanistic study of their formation via pyrolysis and silica-catalyzed process.
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.
Contreras-Torres
Flavio F
FF
Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Circuito Exterior C. U., A. Postal 70-543, 04510 México D.F., Mexico.
Basiuk
Vladimir A
VA
D000596:Amino Acids / Q000737:chemistry*; D002384:Catalysis; D003198:Computer Simulation; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D013816:Thermodynamics
D000596:Amino Acids; D007093:Imidazoles; D011719:Pyrazines; D012822:Silicon Dioxide