NMR Spectroscopic and Theoretical Studies on Tautomerism and Isomerism of Perfluoroalkyl‐Substituted 1,5‐Benzodiazepines

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AbstractThe tautomerism and isomerism of several ethyl 2‐(4‐(perfluoroalkyl)dihydro‐2H‐benzo(naphtho)[b][1,4]diazepin‐2‐ylidene)acetates were investigated by 1H‐, 13C‐, 15N‐ and 19F‐NMR spectroscopy and DFT computations. Depending on the polarity and basicity of the solvent a different behaviour was observed. In CDCl3, (D6)acetone and CD3CN solution two chelate hydrogen bonded tautomers, the enaminoimine and the diaminodiene, were found to exist. In the polar and more basic solvents (D6)DMSO and (D7)DMF two further species, the chelate ring‐opened isomers, were detected. The ratio of the isomers is influenced by the solvents and the substituents at the chelate ring. The chelate enaminoimine is favoured in the less polar chloroform, whereas the chelate diaminodiene predominates with increasing polarity of solvents. The length of the perfluoroalkyl chain and the substituents of the phenyl ring do not influence the isomeric equilibrium as much as the chlorine atom in 4‐position. The structures of the isomers were unambiguously confirmed by one‐ and two‐dimensional techniques (1H,1H‐COSY, 1H,1H‐NOESY (EXSY), 1H,13C‐ and 1H,15N‐chemical shift correlation spectra (HSQC and HMBC)). The observed 15N NMR data are typical for enamines, amides and diazepines and additionally confirm the proposed structures of the four isomers. The time‐dependent course of the equilibration in DMSO solution was followed by recording 1H and 19F spectra. Calculated Gibbs free energies (ΔG) correlate essentially with our experimental findings.