Experimental NMR and MS study of benzoylguanidines. Investigation of E/Z isomerism

Molecules containing the guanidinic nuclei possess several pharmacological applications, and knowing the preferred isomers of a potential drug is important to understand the way it operates pharmacologically. Benzoylguanidines were synthesized in satisfactory to good yields and characterized by NMR, Electrospray Ionization Mass Spectrometry (ESI‐MS) and Fourrier Transform InfraRed Spectroscopy techniques (FTIR). E/Z isomerism of the guanidines was studied and confirmed by NMR analysis in solution (1H‐13C Heteronuclear Single Quantum Coherence (HSQC) and Heteronuclear Multiple‐Bond Correlation (HMBC), 1H‐15N HMBC, 1H‐1H Correlation Spectroscopy (COSY) and Nuclear Overhauser Effect Spectroscopy (NOESY) experiments) at low temperatures. Compounds with p‐Cl and p‐Br aniline moiety exist mainly as Z isomer with a small proportion of E isomer, whereas compounds with p‐NO2 moiety showed a decrease in proportion of isomer Z. The results are important for the application of these molecules as enzymatic inhibitors. Copyright © 2013 John Wiley & Sons, Ltd. NMR and ESI‐MS studies of benzoylguanidines are reported. E/Z isomerism of the benzoylguanidines was confirmed by NMR experiments at low temperatures. These studies indicate that atropisomerism mechanism is responsible for dynamic process in guanidine systems and that the proportion between E/Z isomers is dependent on p‐substituent group on aniline ring.