Decoding the Reaction Mechanism of the Cyclocondensation of Ethyl
acetate 2-oxo-2-(4-oxo-4H-pyrido [1.2-a] pyrimidin-3-yl)
polyazaheterocycle and Ethylenediamine using Bond Evolution Theory
Abstract
The bonding evolution theory has been used to investigate the flow of
electron density along the reaction pathways of ethyl acetate
2-oxo-2-(4-oxo-4H-pyrido [1.2-a] pyrimidin-3-yl) polyazaheterocycle
(1) and ethylenediamine (2). This reaction has three channels (1-3) and
each one takes place via three or four steps. DFT results reveal that
channel 2, which goes through imine intermediate is by far the most
favorable one, and the main product 3 is more stable than 4 and 5,
showing that this reaction is under kinetic and thermodynamic control,
in clear agreement with the experimental outcomes. The BET analysis
allows identifying unambiguously the main chemical events happening
along channel 2. For this reaction channel, the mechanism along the
first step (TS2-a) is described by a series of four structural stability
domains (SSDs), while five SSDs are required for the second (TS2-b) and
the third (TS2-c) one. The first step can be summarized as follow, the
appearance of V(N1,C6) basin illustrating the formation of N1-C6 bond
(SSD-II), the splitting of N1-H1 bond, followed by the restoration of
the nitrogen N1 lone pair (SSD-III), and finally, the formation of the
last O1-H1 bond (SSD-IV). For the second step, the formation of
hydroxide ion is noted, consequent of the disappearance of V(C6,O7)
basin, the transformation of C6-N1 single bond into double one (SSD-IV).
Finally, the appearance of V(O7,H2) basin leading to the elimination of
water molecule within the last domain. Overall, for the three reaction
steps, the formation of the N-C bond appears always before the O-H one.