Banca de DEFESA: GABRYELLE CARVALHO MARÇAL SALGADO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : GABRYELLE CARVALHO MARÇAL SALGADO
DATE: 13/12/2023
TIME: 14:00
LOCAL: Sala C 3.15
TITLE:

"Theoretical Investigation of the Generation, Stability and SNAr Reactivity of KCF3 Complexed with 18-Crown-6"

KEY WORDS:

Trifluoromethylation Reactions. Phase Transfer Catalysis. KCF3(18C6) Complex

PAGES: 112
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

 While fluorine is one of the most abundant elements in the Earth's crust, fluorinated organic compounds are rarely found in nature and biological processes. The significance of incorporating fluorine into organic compounds lies in its ability to enhance the effectiveness of these substances by altering their chemical and physical properties. With the aim of elucidating a synthetic process for the production of trifluoromethylated products, the thermodynamic and kinetic feasibility of trifluoromethylation reactions in aryl substrates was investigated using phase-transfer catalysis with 18C6 crown ether as the catalyst. The research covered everything from the generation, stability, and reactivity of the KCF3(18C6) complex to the formation of trifluoromethylated products resulting from the SNAr reaction, including the analysis of the free energy profile throughout the entire catalytic cycle. The study involved computational simulations using DFT with the ωB97X–D3 and ωB97M–V functionals, the def2–SVP, ma–def2–SVP, and def2–TZVPP functions, as well as the SMD solvation model. To obtain trifluoromethylated products, the process was catalyzed by phase transfer, employing 18C6 crown ether as the catalyst. In this context, the catalytic species promotes complexation with the ionic solid, allowing its solubilization in the organic solvent and providing the anion (OH– or CH3O–) with greater freedom to act as a nucleophile. Furthermore, it stabilizes the KCF3 species and accelerates the SNAr reactions. The first step of the catalytic cycle involves dissolving the ionic salts, KOH and CH3OK, followed by the formation of the KCF3(18C6) complex through the reaction of the ionic solid with the trifluoromethyl sources, TESCF3 and HCF3. The process with KOH was not thermodynamically viable as it did not result in the formation of the KCF3(18C6) species; the synthesis halted due to the formation of an unwanted intermediate. In this regard, the process involving KOH reacting with HCF3 was not described due to the inefficacy of the reaction with TESCF3.When the process is carried out with the solid CH3OK, a high concentration of the KCF3(18C6) species is formed, with a free energy ΔG‡ of –19.9 kcal mol-1. However, when the mechanism involves CH3OK with HCF3, the process results in the formation of the nucleophilic species, albeit in lower concentration, with a ΔG‡ of 5.8 kcal mol-1. Therefore, the formation of KCF3(18C6) is favored through CH3OK and TESCF3. After the nucleophile is generated, the next step in the cycle involves SNAr reactions with the substrates. However, it's possible for the nucleophile to undergo decomposition, interact with water, TESCF3, or experience deprotonation of the catalyst. Thus, if the reaction is conducted in an anhydrous environment and the transition state barriers for nucleophile insertion are lower than the free energy of decomposition of the KCF3(18C6) dimer, which corresponds to 18.7 kcal mol-1, the SNAr reactions will proceed without competition from nucleophile decomposition.Among the investigated substrates, PhBr, p-CNArBr, p-NO2ArBr, m,p-(CN)(NO2)ArBr, o,p-(CN)(NO2)ArBr, o,p-(CN)2ArBr, o,p-(NO2)2ArBr e o-NO2ArF, those more reactive than decomposition are the doubly activated compounds and the compound with fluorine as the leaving group. Kinetic analysis revealed that the lower the transition state barrier in the SNAr reaction, the more rapidly the reaction is favored to occur, justifying this barrier as the determining step in the cycle's speed. Through the studies in this work, the ideal catalytic cycle involves the formation of KCF3(18C6) via CH3OK and TESCF3, followed by the subsequent SNAr reaction with doubly activated substrates to avoid competition with nucleophile decomposition.

BANKING MEMBERS:
Presidente - 1623600 - JOSEFREDO RODRIGUEZ PLIEGO JUNIOR
Interno - 1727278 - LUIZ GUSTAVO DE LIMA GUIMARAES
Externo à Instituição - HEITOR AVELINO DE ABREU - UFMG