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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
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Fluoro, Trifluoromethyl, and Trifluoroacetyl Substituent Effects on Cycloaddition Reactivities: Computations and
Ruirui Su1, Kaili Xie1, Yong Liang2
1College of Sciences, Nanjing Agricultural University, Nanjing210095, China.
Abstract:
The importance of fluoro and trifluoromethyl substituents in drug effectiveness prompted the computational exploration of fluorine-containing substituents in valuable synthetic cycloadditions. Diels-Alder or 1,3-dipolar cycloaddition reactions of typical reactants, cyclopentadiene, N-phenyldiazoacetamide, tetrazine, and N-phenylsydnone involving fluorine-containing substituents (F, CF3, and COCF3) were studied with M06-2X density functional theory. Inductive and conjugative effects influence normal and inverse electron-demand reactions differently. These results provide a guide to the design and use of cycloadditions for the introduction of fluoro and trifluoromethyl substituents in synthetic processes.
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Stability of Substituted Cyclohexanes
The two chair conformations of cyclohexanes undergo rapid interconversion at room temperature. Both forms have identical energies and stabilities, each comprising equal amounts of the equilibrium mixture. Replacing a hydrogen atom with a functional group makes the two conformations energetically non-equivalent.
For example, in...