Thermal reactions of cyclohexen-1,3-oxazine and 1,3-thiazine cis-fused studied from green metrics.

PINILLA PEÑA, DIANA C.; SZAKONYI, ZSOLT; PELÁEZ, W. J.

Venezia

Encuentro; GREEN CHEMISTRY POSTGRADUATE SUMMER SCHOOL, 3rd ? 8th July 2022; 2022

GREEN CHEMISTRY POSTGRADUATE SUMMER SCHOOL, 3rd ? 8th July 2022

The study of the thermal reactions of 1,3-oxazines and 1,3-thiazines is of great interest due to the different pharmacological properties of these compounds.1,2 In order to obtain information on the thermal stability of cis-cyclohexen-fused 1,3-heterocycles,3,4 as compounds 1, 2, 3 and 4 present in Figure 1, flash vacuum pyrolysis (FVP) reactions between 300-500ºC were carried out. In addition to these reactions, a green assessment was carried out to identify the impact of the study of pyrolysis reactions on the environment. This study was carried out using two recognised methodologies for this evaluation, namely Green Star5,6 and Ecoscale6 . Table 1 presents the results of the Green metric assessment of 1,3-oxazine and 1,3-thiazine compounds.Table 1. Green parameters of 1,3-oxazine and 1,3-thiazines studied. ........ . Figure 1.Sust.Yield %aGSAI%EcoScaleMIRMEAEE 110075,50812,68276,622,0254,3065,0058,153,545,377,862,5354,9066,2558,452,340,2379,063,245,6075,5033,85,63,2077,672,0a.percentage yield of pyrolysis product after isolation and purification, calculated at 475°C.The Arrhenius parameters characterising these thermolysis processes show that: -the Ea and ΔH# for the N-substituted compounds are higher than for their hydrogenated counterparts, -all processes occur with negative entropic changes, -due to the high temperatures employed, the entropic term is not negligible and the reaction mechanism must be proposed as a function of the ΔG# , the observed differences in the ΔG# allow multiple competitive reactions to be proposed, of which the retro Diels Alder reaction (RDA) is the most interesting from a mechanistic point of view.In the evaluation of the thermolysis table 1, it was determined that the reaction conditions in which the principles of green chemistry are best fulfilled, is the use of substrate 1, since it presents better values of atomic economy, low production of residues and derivatization. On the other hand, the low use of solvents for the isolation and purification of the products is highlighted. Similarly, it should be noted that in PVP processes, energy expenditure is minimised by the minimal or almost non-existent use of solvents or purification methods, since the reactions studied present only one product in general, and a similar reaction mechanism. References 1. Mendes de Brito, M.R.; Peláez, W.J.; Faillace, M.S.; Militão, G.C., Almeida, J.; Argüello, G.A.; Szakonyi, Z.; Fülöp, F.; Salvadori, M.C.; Teixeira, F.S.; Freitas, R.; Pinto, P.; Mengarda, A.; Silva, M.; Da Silva Filho, A.; De Moraes, J. Toxicol. Vitr. 2017, 44, 273-279. 2. Firpo, G.; Ramírez, M.L.; Faillace, M.S.; Mendes de Brito, M.R.; Correia Lima e Silva, A.P.; Pereira Costa, J.; Rodríguez, M.C.; Argüello, G.A., Szakonyi, Z.; Fülöp, F.; Peláez, W.P. Antioxidants, 2019, 8(6), 197, 1-14. 3. Peláez, W.J.; Szakonyi, Z.; Fülöp, F.; Yranzo, G.I. Tetrahedron 2008, 64, 1049-10574. D. C. Pinilla Peña, E. N. Ruiz Pereyra, G. Firpo, N. M. Ceballos, F. Fülöp, Z. Szakonyi, A. G. Iriarte and W. J. Peláez. Eur.J. Org.Chem.2021, 11, 1704-1713. 5. Anastas, P.; Eghbali, N. Green Chemistry: Principles and Practice. Chem. Soc. Rev. 2009, 39 (1), 301. 6. Andraos, J. Critical Evaluation of Published Algorithms for Determining Environmental and Hazard Impact Green Metrics of Chemical Reactions and Synthesis Plans. ACS Sustain. Chem. Eng. 2016, 4 (4), 1934-1945.