Using Chou’s 5-Step Rule to Evaluate the Stability of Tautomers: Susceptibility of 2-[(Phenylimino)-methyl]-cyclohexane-1,3-diones to Tautomerization Based on the Calculated Gibbs Free Energies

Abstract

Gibbs free energies, based on DFT (Density Functional Theory) calculations, prove that enaminone (2-(anilinemethylidene)cyclohexane-1,3-dione) and ketamine (2-[(phenylimino)-methyl]cyclohexane-1,3-dione) are the most and least stable tautomeric forms of the studied systems, respectively. 1H and 13C NMR spectra prove that 2-(anilinemethylidene)cyclohexane-1,3-diones are the only tautomeric species present in dimethylsulfoxide solution (a very weak signal can be seen only for the p-methoxy derivatives). The zwitterionic character of these enaminones is strengthened by naphthoannulation and by the insertion of the electron-withdrawing substituent into the benzene ring (the latter weakens the intramolecular hydrogen bond in the compound). Substituent and naphtoannulation have no effect on the stability of the studied tautomers. Slight twisting of the benzene ring, with respect to the CArNC plane (seen in the crystalline state), was proven to also take place in vacuum and in solution.

A Spectroscopic Overview of Intramolecular Hydrogen Bonds of NH…O,S,N Type

“…11.89 ppm [12], whereas an OH group in the ortho-position of a phenyl group at the nitrogen also leads to drop [16], but in this case it is a combination of a twist of the phenyl ring and a field effect caused by the OH group. In case of the o-hydroxyphenyl derivative, Rodríguez et al [17] also report the finding of the keto-form at low concentration in the 1 H-NMR spectrum but not in the 13 [19], of gossypol [22,23] or more recently of primarily on the NH form (2-(anilinemethylidenen)cyclohexane-1,3-dione) [24]. A classic comparison is that of hydrogen bonding involving a ketone or an ester is seen in Figure 5A,B.…”

“…NH chemical shifts may for hydrogen bonded hydrazo com values as high as 15.8 ppm when the NH is hydrogen-bonded to a pyridin [31]. The amine is from [24].…”

“…This is true for the following salicylaldehydes with substituents as follows: 5-nitro, 5-methylcarboxylate, 4-fluor, 4-choro, 4-bromo, 4-methoxy, 4-amino and 5-phenylazo [ 1 ]. A few other examples of compounds entirely on the NH form are Schiff bases of 1,3,5-triacyl-2,4,6-trihydroxybenzene [ 19 , 20 , 21 ], 1,3,5-triformyl-2,4-6-trihydroxybenzene [ 19 ], of gossypol [ 22 , 23 ] or more recently of primarily on the NH form (2-(anilinemethylidenen)cyclohexane-1,3-dione) [ 24 ].…”

Novel Schiff Bases of C-Methylresorcinarene Derivatives

“…All proton signals are strongly broadened, which is associated with tautomerism. However, the spectra only show one set of signals, which suggests a fast tautomeric exchange [18,19].…”

Synthesis of 1‐phenyl‐3‐(quinolin‐8‐ylamino)prop‐2‐en‐1‐one and analysis of its structure by X‐ray crystallography, NMR, UV‐Vis spectroscopy and DFT calculations

“…[19] A large amount of evidence has been collected using NMR, UV, IR spectroscopy as well as X-ray crystallography which showed that the most of the βenaminones exists in the tautomeric enaminoketone form. [19][20][21] The structure of the molecule, the electronic contribution and volume of substituents, intramolecular hydrogen bonds, temperature and solvent polarity affects both the tautomerization process and the isomerization process. [22] Tautomerization processes lead to a rearrangement of electronic levels, which to some extent affects other properties of molecular systems.…”