With fluorine becoming increasingly important in bioactive compounds, trifluoromethyl ethers are more commonly used in agrochemicals and pharmaceuticals.Contrary to the traditional etherification methods, the new synthesis of trifluoromethyl ether involves a nucleophilic attack of a carbanion on an electrophilic oxygen. The schemes of our specific calculations show the Gringard reagent inserting itself between the peroxide oxygens of trifluoromethyl peroxyacetal or trifluoromethyl perbenzoate and the nucleophilic carbon approaching a peroxide oxygen, followed by a cleavage to form an ether. The geometry of each molecule in the schemes was optimized using the B3LYP/6-31+G(d,p) model chemistry in THF. The quantum calculations, in conjunction with the experimental data from Dussault et al., show that the wanted trifluoromethyl ether is the most likely product for peroxy acetals since it has an activation energy 5.7 kcal/mol lower than the next most likely pathway. However, the effectiveness of using perbenzoates is debatable since the computational results point to the trifluoromethyl ether as product with the highest yield, which stands contrary to the 19F NMR data of the final product. Perester of m-chloroperbenzoic yield similar results to those of perbenzoate computationally and experimentally. Further computational calculations of 19F NMR shifts could reveal the product set.

Quantum calculations of bimolecular etherification reaction of trifluoromethyl peroxides and Grignard reagents

255th National Meeting (2018)

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