Banca de DEFESA: PAULO VITOR MATIAS FARIA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : PAULO VITOR MATIAS FARIA
DATE: 03/01/2022
TIME: 14:00
LOCAL: VIDEO CONFERENCIA
TITLE:

Computational Modeling of the Reaction of the Pyrrolidine with Pyridine-N-Oxide Activated by Phosphonium Salt: Electrostatic Control Of Regioselectivity.

KEY WORDS:

Modeling,DFT,synthesis,2-aminopyridines,effect,Counter-ion

PAGES: 67
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Físico-Química
SPECIALTY: Química Teórica
SUMMARY:

Aminopyridines belong to an important class of compounds in organic chemistry, due to their applications in the construction of drugs particularly related to neurological diseases. In 2010 an alternative, general, easy and one-pot method was presented for the synthesis of 2-aminopyridines from pyridine-N-oxides activated with phosphonium salts. This alternative method showed high efficiency and selectivity when compared to the conventional preparation method. In this work, the mechanism of this synthesis was elucidated through quantum calculations of electronic structure, using the density functional theory and the continuous solvation model. We are proposing that the mechanism of this reaction be described in four steps and that the regioselectivity be kinetically controlled, but not thermodynamically. First, the pyridine-N-oxide is added to the phosphonium salt from a nucleophilic displacement, forming a first reaction intermediate (a phosphonium complex with a double positive charge). Second, this first intermediate undergoes an amine attack, which can occur either at position 2 or at position 4 of the activated pyridine-N-oxide. Finally, two subsequent proton abstractions must produce 2- and/or 4-aminopyridines. Our computational results suggest that counterions, which are derived from the phosphonium salt, play a key role in the regioselectivity of these reactions. We found that 4-aminopyridine formation is slightly favorable when the reaction path is modeled without the presence of counterions. However, when counterions were considered in the reaction mechanism, we observed that the pathway related to the attack at position 2 of pyridine-N-oxide becomes preferential, presenting more accessible reaction barriers and exergonic reaction intermediates. The regiochemical preference for the addition of the 2-position can be attributed to a charge association that occurs between the reactional intermediate of the phosphonium complex and the counterions. Furthermore, we verified a critical dependence of the evolution of this reaction with some characteristics of the phosphonic additive. In this case, the phosphonium salt must have a good leaving group for the pyridine-N-oxide activation step to occur easily.

BANKING MEMBERS:
Externa à Instituição - ELIZETE VENTURA DO MONTE - UFPB
Interno - 1803692 - FABRICIO GAVA MENEZES
Presidente - 1859346 - MIGUEL ANGELO FONSECA DE SOUZA