Determination of the second-order 1H NMR parameters for the aromatic protons in 4-fluoroaniline and application to the analysis of the 1H NMR spectra for the aromatic protons in N4-(4′-fluorophenyl)succinamic acid and in N4-(4′-fluorophenyl)-3,3-difluoros

Four studies of the 1H NMR spectrum for the aromatic protons of 4-fluoroaniline between 1958 and 1974 give three very different solutions to the second-order, AA′BB′X, spectrum. A re-evaluation of the second-order spectrum was done at 300 MHz. Simultaneous simulations of the 1H NMR spectrum and 19F NMR spectrum for 4-fluoroaniline were done using WINDNMR-Pro, and a new set of parameters for the six coupling constants was obtained from the optimized simulations. This new set of parameters was used as a basis to evaluate the AA′BB′X spectrum for the aromatic protons in N4-(4′-fluorophenyl)succinamic acid and in N4-(4′-fluorophenyl)-3,3-difluorosuccinamic acid by simultaneous simulations of the 1H NMR spectrum and 19F NMR spectrum for each using WINDNMR-Pro. Formation of the amide bond results in small, but significant, changes in the values for the set of parameters in both molecules. These results confirm that second-order analyses as an AA′BB′X system are required for derivatives of 4-fluoroaniline, rather than first-order analyses that have been used in previous reports.

Graphical abstractOptimized simulation of a 1H NMR second-order, AA′BB′X, spectrum for the aromatic protons in a para-fluoroanilide using WINDNMR-Pro.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Re-evaluation of the second-order, AA′BB′X, 1H NMR spectrum for 4-fluoroaniline. ► Simultaneous simulations of the 1H and 19F NMR spectra using WINDNMR-Pro. ► New set of NMR parameters for 4-fluoroaniline. ► Second-order, AA′BB′X, NMR parameters obtained for succinamic acid 4′-fluoroanilide.