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

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 1H, 13C, and 19F NMR, EI–MS, and IR data of 3 and 4. Empirical parameters and DFT calculations are used to predict the 1H and 13C NMR chemical shifts of 4 and the hypothetical brominated analogue.

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