Use of H-1, C-13, and F-19-NMR Spectroscopy and Computational Modeling To Explore Chemoselectivity in the Formation of a Grignard Reagent

摘要

A discovery-based Grignard experiment for a second-year undergraduate organic chemistry course is described. The exclusive Grignard reagent formed by the reaction of 1-bromo-4-fluorobenzene (1) with Mg is 4-fluorophenylmagnesium bromide (2), which is treated with either benzophenone or CO2 to produce the corresponding fluorinated alcohol (3) or benzoic acid (4), respectively. The use of a dihalogenated Grignard reagent requires students to discern its reactivity for synthesis. Students predict the. chemoselectivity of Grignard reagent formation based on the C-X bond energies of 1 and investigate their predictions by analysis of H-1, C-13, and F-19 NMR, EI-MS, and IR data of 3 and 4. Empirical parameters and DFT calculations are used to predict the H-1 and C-13 NMR chemical shifts of 4 and the hypothetical brominated analogue.