A DFT computational study on the [ 3 + 2 ] cycloaddition between parent thionitrone and nitroethene

Article history: Received December 22, 2017 Received in revised form January 29, 2018 Accepted February 15, 2018 Available online February 15, 2018 A molecular mechanism of the [3+2] cycloaddition has been explored using various DFT theoretical levels. It was found that the reaction proceeds via transition states with different synchronicity, but no intervention of the theoretical possible zwitterionic intermediates. Additionally, regioselectivity of the cycloaddition process has been analysed using vibrational analysis of localised TSs. © 2018 Growing Science Ltd. All rights reserved.


Introduction
2][3][4][5] Heterocyclic compounds with two different heteroatoms particularly are the object of growing research interest of chemists.][8][9][10] The isothiazole ring is present in compounds with biological activity such as the pharmaceutical drugs ziprasidone and perospirone. 11,12[19][20] Nitroisothiazolidines can be prepared via [3+2] cycloaddition reaction involving thionitrones and conjugated nitroalkenes as addents.Unfortunately, there has been no relevant research so far dedicated the cycloaddition reaction of conjugated nitroalkenes with thionitrones.Moreover, chemistry thionitrones is nearly unknown today. 21This work initiates the comprehensive study in this area.
Depending on the condition and nature of the reagent, the studied reaction (Scheme 1.) may furnish two isomeric products following the path A or B. The structure of the product could be predicted based on quantum chemical studies of the reaction mechanism we are presented herein.Scheme 1. Theoretically possible paths of [3+2] cycloaddition reaction between parent thionitrone and nitroethene.

Computational details
For the simulation of the reaction paths hybrid functional B3LYP with the 6-31G(d), basis set included in the GAUSSIAN 09 package 22 was used.4][25][26] The critical points on reaction paths were localized in an analogous manner as in the case of the previously analyzed reaction of diazafluorene with cyanonitroethenes. 26In particular, for structure optimization of the reactants and the reaction products the Berny algorithm was applied.Firstorder saddle points were localized using the QST2 procedure.The TSs were verified by diagonalization of the Hessian matrix and by analysis of the intrinsic reaction coordinates (IRC).In addition, similar simulations using more advanced B3LYP/6-31+G(d), B3LYP/6-31G(d,p) theoretical levels were performed.For optimized structures the thermochemical data for the temperature T = 298K and pressure p = 1 atm were computed using vibrational analysis data.
Indexes of -bonds development (l) were calculated according to the formula 27 : TS 1  , where r TS A-B is the distance between the reaction centers A and B at the TS and r P A-B is the same distance at the corresponding product.
The kinetic parameters as well as essential properties of critical structures are displayed in Tables 1  and 2.

Scheme 2. Mechanism of [3+2] cycloaddition reaction between parent thionitrone and nitroethene
The results obtained from B3LYP/6-31G(d) calculations show that energy profiles of both considered reactions are similar.In particular, between the valley of starting materials and the valley of final product, only one maximum of the transition state (TS) was localized.Additionally, before the transition state, a valley of pre-reaction complex was identified (Table 1, Fig. 1).All attempts of localization of alternative transition states which may be connected with hypothetical zwitterionic mechanism, were not successful.Interactions of addents at first lead to formation of the pre-reaction complex MC.This is a common intermediate for both considered reaction channels.The formation of MC is accompanied by a reduction of the enthalpy system by about 3.5kcal/mol.MC however may not exist as a stable intermediate, because Gibbs free energy of its formation is positive.Within the MC, any new bonds are not formed.Distances between reaction centres (Table 2) exist beyond areas, typical for new bonds in the transition state.
Table 2. Key parameters of critical structures for [3+2] cycloaddition between parent thionitrone (1) and nitroethene (2) according to DFT calculations.A further conversion of MC on both considered paths lead to the transition state (TSA for path A, and TSB for path B).This is accompanied by an increasing of the enthalpy by 1.8 kcal.mol and 3.5 kcal/mol for paths A and B respectively.Subsequently, entropy of the reaction system dramatically decreased.In consequence, Gibbs free energies of the activation are equal 14.8 kcal/mol and 16.5 kcal/mol for paths A and B respectively.Thus, the regioisomeric channel leading to the 4-nitroadduct (3) is favoured, however both theoretically possible paths should be considered as if it was allowed from the kinetic point of view.Within TSs two new sigma bonds are formed.There are C3-C4 and C5-S1 bonds.These bonds are formed simultaneously, however the degrees of their development are different.In particular, the more synchronous is less favoured by TS on the path B (l=0.03).

Interatomic distances
A further transformation of TSs lead to a valley which should be connected with the final product.This was confirmed by the IRC calculations.A similar picture of the considered reaction provides analogous DFT calculations on more advanced theoretical levels (Tables 1 and 2).

Conclusions
The DFT calculations, independently of theoretical level suggest that a favoured direction of [3+2] cycloaddition between parent thinitrone and nitroethene is the reaction leading to the 4-nitro-1,2thiazolidine. Competitive reaction channels leading to the 4-nitro-1,2-thiazolidine are less favoured, but allowed from the kinetic point of view.A detailed exploration of the reaction paths confirmed without any doubts that all competitive reactions should proceed according to a one-step, but asynchronous mechanism.The synchronicity of the formation of new sigma bonds is depends on the orientation of addents substructures in the transition state.