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 CO 2 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 1 H, 13 C, and 19 F NMR, EI–MS, and IR data of 3 and 4 . Empirical parameters and DFT calculations are used to predict the 1 H and 13 C NMR chemical shifts of 4 and the hypothetical brominated analogue.